Atroposelective Synthesis, Structure and Properties of a Novel Class of Axially Chiral N‐Aryl Quinolinium Salt

Abstract

Inspired by naturally occurring molecules containing atropisomeric N+‐C axes, we have developed a novel synthetic approach to generate a library of axially chiral N‐aryl quinolinium salts. Enantiopurities up to 93 % ee were obtained via a four‐step route from commercially available precursors. Axial stereochemistry was controlled through an enantioselective ring‐closing Buchwald–Hartwig coupling reaction. The structure and properties of the salts were examined by X‐ray crystallography, DFT, UV‐Vis, and fluorescence spectroscopy, revealing high rotational barriers and solvatochromic behaviour.

Catalytic Enantioselective Synthesis of C–N Atropisomeric Heterobiaryls

“…Enantioselective synthesis of N-arylquinolin-4-ones enroute to N-arylquinolinium salts. 17 The absolute stereochemistry of the major product is determined by comparison of optical rotation data for R = t-Bu, Ar = Ph with a previous report by Kitagawa. 15 The Kitagawa group further extended the repertoire of palladium-catalysed atroposelective ring-closure to the synthesis of N-arylphenanthridin-6-ones (Scheme 10).…”

“…Scheme 8 Synthesis of N-arylquinolin-4-ones using a palladium-catalysed asymmetric ring-closure 15 Knipe and co-workers used a similar strategy to afford N-arylquinolin-4-ones en route to cationic chiral Narylquinolinium salts (Scheme 9). 17 Using as substrates the enaminones 38 presumed as intermediates in the Kitagawa study above, they obtained a series of N-(2-tert-butylphenyl)-and N-naphthylquinolin-4-ones 39 under optimised conditions using Pd(OAc) 2 and (R a )-BINAP in high yields (up to 99%) and variable enantioselectivity (up to 82% ee). A curious enantiodivergence was observed during optimisation: use of (R a )-BINAP led to opposite product enantiomers depending on the palladium source.…”

The Asymmetric Buchwald–Hartwig Amination Reaction

“…Later, Knipe reported the use of asymmetric Buchwald-Hartwig reactions en route to axially chiral N-arylquinolinium salts (Scheme 18b). [68] Enaminones 57 were treated with a palladium/(R)-BINAP catalyst to deliver enantioenriched Narylquinolin-4-ones 56 with ees of up to 82 %. Both efficiency and enantioselectivity depended on the electronic and steric nature of the substituent.…”

Efficient Synthesis of 7H‐Chromeno[3,2‐c]quinolin‐5‐ium Salts and Quinolin‐4‐ones through Acid‐Promoted Cascade Reaction of 3‐Formylchromones and Anilines

“…This core structure is present in natural products such as alkaloid cryptolepine [1] and nitidine [2] (Figure 1). Quinolinium salts have attracted much interest as essential scaffolds found in many biologically active molecules, [3–5] pharmaceuticals, [6–7] and material applications [8–11] . Owing to its strong oxidizing ability at a singlet excited state, quinolinium salts are interesting from theoretical and practical perspectives, and also they can be used as starting materials in organic reactions to construct heterocyclic compounds with special structures [12–17] .…”